Abstracts

Rationale: The Pediatric Epilepsy Research Consortium (PERC) developed a special interest group (SIG) dedicated to genetic epilepsies. Individually, many of the genetic epilepsies are rare, and cases are dispersed across tertiary epilepsy centers. This has been a patient barrier to accessing research, as well as community understanding of specific disorders, as pathways to these studies have been through large single-center cohorts or through orphan disease organizations.  PERC created a genetic database to record known pathogenic variants and variants of unknown significance for children with epilepsy. The specific aims are: 1) to build a platform for capturing specific clinical data elements to facilitate understanding of the natural history, and 2) facilitate recruitment for future studies and clinical trials.

Methods: The PERC Genetics SIG initially developed a list of data elements, which were selected for compilation in a REDCap database. Families of children with epilepsy can be approached for consent to participate if the child has an identified pathogenic variant or variant of unknown significance. The genetic data include clinically available testing methods (e.g. CGH, panels, whole exome sequencing). Variants are recorded by standard cytogenetic reporting standards, or in the case of single gene disorder, changes to both nucleic acid and protein structure, with the reference transcript ID. Clinical elements include age of onset, seizure type (motor vs non-motor), presence of status epilepticus, number/names of treatments, and comorbidities. Additional clinical features may be pulled into the entry by linking with the Human Phenotype Ontology (HPO).  Participants may opt-in for annual surveys for up to 10 years to update seizure frequency, treatments, seizure emergencies, and comorbidities and may also opt-in to be contacted for additional studies.

Results: The database went into production in March 2022. Two centers have received IRB approval and are actively recruiting patients. Two additional sites have pending IRB approval. The anticipated prospective recruitment rate per center is 3-4 participants/month, and participating centers have >100 retrospective cases each, which also meet criteria for enrollment.

Conclusions: The PERC Genetic Epilepsy Database complements existing research approaches to genetic epilepsies. Potential advantages of this approach include broad geographic inclusion amongst participating PERC centers, facilitation of access to research opportunities, potential for hypothesis generation regarding comparative effectiveness of treatments, pathway for understanding natural history in disorders without a current champion in the rare disease community, and prospective collection of rates of variant reclassification.

Funding: Not applicable